Brunner M C, Mitchison N A
Cancer Research Laboratories, University of California at Berkeley, USA.
Immunology. 1996 Jul;88(3):452-5. doi: 10.1046/j.1365-2567.1996.d01-670.x.
Although rapid progress is being made in the quantitative genetics of multifactorial disease, no response to a simple antigen has yet been subjected to full genomic analysis. The well-characterized antigen allo-HPPD (4-hydroxy-phenylpyruvate dioxygenase, previously known as F liver antigen) is a good candidate for such treatment. Old and new data bearing on this possibility are here assembled. In respect of antibody production and an early burst of interleukin-4 (IL-4) transcription, introduction of the non-major histocompatibility complex (MHC) background from A/J strain mice into F1 hybrids with C57BL10 strains up-regulates the response. These findings can be aligned with previous quantitative genetics carried out on airway hyper-responsiveness in related strains, and to a lesser extent with the genetics of autoimmune diabetes in the mouse. Taken together, the findings suggest that regulation of the pro-inflammatory cytokines are largely responsible for the variation. Additional data indicate that these non-MHC genes are are to a variable extent (depending on the response parameter) epistatic to the down-regulatory MHC allele H-2Ab.
尽管在多因素疾病的数量遗传学方面正在取得迅速进展，但对简单抗原的反应尚未进行全面的基因组分析。特征明确的抗原异源HPPD（4-羟基苯丙酮酸双加氧酶，以前称为F肝脏抗原）是进行此类研究的良好候选对象。本文收集了与这种可能性相关的新旧数据。在抗体产生和白细胞介素-4（IL-4）转录早期爆发方面，将A/J品系小鼠的非主要组织相容性复合体（MHC）背景引入与C57BL10品系的F1杂种中，可上调反应。这些发现可以与之前对相关品系气道高反应性进行的数量遗传学研究结果相呼应，在较小程度上也与小鼠自身免疫性糖尿病的遗传学研究结果相符。综合来看，这些发现表明促炎细胞因子的调节在很大程度上导致了这种变异。其他数据表明，这些非MHC基因在不同程度上（取决于反应参数）对下调性MHC等位基因H-2Ab具有上位性。
